Preparation and use of photopolymerized microparticles

Abstract

Methods of forming crosslinked polymer particles in situ from polymer precursors such as monomers or oligomers, comprising exposing a composition comprising at least one polymer precursor, a solvent or solvent mixture, and an antisolvent or antisolvent mixture to photoradiation under conditions whereby particles are formed are provided. The polymer precursor may be photosensitive, or a separate polymerization initiator may be used. In a preferred embodiment, the polymer precursor is insoluble in the antisolvent or antisolvent mixture and the solvent or solvent mixture is soluble in the antisolvent or antisolvent mixture at the concentrations used. Crosslinked polymer particles and crosslinked polymer particles comprising a polymer and a bioactive material are also provided. The polymer may be erodable, and the polymer particles formed may be used in a variety of applications, including controlled release of bioactive materials such as drugs. Polymer particles formed using the methods of the invention have low residual solvent levels and high additive encapsulation efficiencies. The processes of the invention allow control of particle size and morphology, use low operating temperatures and are useful for efficient bulk production.

1. A method for making crosslinked polymer particles with a desired double bond conversion amount comprising the steps of:
 exposing a composition comprising a polymer precursor, a non-aqueous solvent or solvent mixture, and an antisolvent or antisolvent mixture to photoradiation under conditions whereby crosslinked particles of the desired conversion amount are formed, wherein the antisolvent is a supercritical or near supercritical fluid in which the polymer precursor is not substantially soluble.  
 
     
     
       2. The method of  claim 1 , wherein the double bond conversion amount is between about 70% and 100%. 
     
     
       3. The method of  claim 1 , wherein the double bond conversion amount is between about 20% and about 100%. 
     
     
       4. The method of  claim 1 , wherein the polymer precursor has a carbon-carbon double bond functional group. 
     
     
       5. The method of  claim 4 , wherein the carbon-carbon double bond functional group is selected from the group consisting of acrylates and methacrylates. 
     
     
       6. The method of  claim 1 , further comprising the step of washing the particles with supercritical fluid, whereby the polymer particles comprise less than about 1% of residual solvent. 
     
     
       7. A method for making crosslinked polymer particles having a desired network mesh size comprising the steps of:
 selecting a polymer precursor;  
 determining a double bond conversion amount which corresponds to the desired network mesh size for the polymer;  
 exposing a composition comprising the polymer precursor, a non-aqueous solvent or solvent mixture, and an antisolvent or antisolvent mixture to photoradiation under conditions whereby crosslinked particles having the double bond conversion amount are formed, wherein the antisolvent is a supercritical or near supercritical fluid in which the polymer precursor is not substantially soluble and whereby the crosslinked particles have the desired network mesh size.  
 
     
     
       8. The method of  claim 7  wherein the network mesh size is between about 10 and about 500 Angstroms. 
     
     
       9. The method of  claim 7 , wherein the polymer precursor has a carbon-carbon double bond functional group. 
     
     
       10. The method of  claim 9 , wherein the carbon-carbon double bond functional group is selected from the group consisting of acrylates and methacrylates. 
     
     
       11. The method of  claim 7 , further comprising the step of washing the particles with supercritical fluid, whereby the polymer particles comprise less than about 1% of residual solvent.